A couple of average height has a newborn with rhizomelic shortening of the limbs, a prominent forehead, midface hypoplasia, and macrocephaly with a narrow thorax. Radiographs show short long bones with flared metaphyses. Which statement about this condition is correct?

• A It results from gain of function of FGFR3, and sporadic cases correlate with advanced paternal age ✓
• B It results from loss of function of FGFR3, and sporadic cases correlate with advanced maternal age
• C It results from collagen type II deficiency, and homozygosity improves survival
• D It results from gain of function of FGFR2, and recurrence risk in siblings is 50 percent

Explanation

Achondroplasia, the commonest cause of disproportionate short stature, arises from activating mutations of FGFR3, usually the Gly380Arg substitution, which constitutively inhibits chondrocyte proliferation in the growth plate. About 80 percent of cases are sporadic, and de novo mutations show a strong paternal age effect because they originate in spermatogonial divisions. Homozygous achondroplasia is perinatally lethal from the narrow thorax, and FGFR2 gain of function causes apert syndrome rather than this skeletal dysplasia.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.